There are many wonderful regioselective reactions, but it is interesting to see how they invented different reactions because they could not get the selectivity they were looking for. The final highlight is the allyl oxidation (?) by SET. I am happy to see the hard work pay off in this way.
Reactions where the selectivity was reversed are IMDA (exo addition ➞ end addition at low temperature with Lewis acid catalyst), isomerization by HAT reduction (intramolecular 1,5 shift ➞ suppression by functional group conversion), ketone α-deprotonation (protection as MOM enol ether), dehydration (exo direction ➞ end direction by dehydrogenation, dehydration, and 1,4 reduction), and epoxidation (from less hindered side ➞ from more hindered side by blocking with the solvent).
I don’t know what they were planning for the oxidation of the allyl moiety at the end, but when it is subjected to enolate-forming conditions, an intramolecular redox reaction occurs (releasing HBr) and the final product is suddenly obtained. The reaction mechanism has been studied in detail using model compounds.
There are some references to old papers by Dr. Barton (e.g. the photosantonin rearrangement).
Two-phase synthesis (cyclase + oxidoreductase). Aromatic rings of intermediates are oxidized and converted to various related natural products.
It can be said that this is a total synthesis that demonstrates the high functionality of the building block produced by asymmetric cross-coupling. It contains a quaternary chiral center and all four functional groups that can be manipulated orthogonally.
The radical reaction with the phthalimide ester, which was expected to be active as a redox catalyst, failed under redox conditions. Finally, AIBN-Bu3SnH was used for successful radical cyclization to form an ethylene bridge.
They struggled with the process of making the amide by intramolecular condensation after a one-carbon extension of the nitrile. They finally succeeded in creating an efficient route to the amide using TosMIC.
First of all, the 14-step synthesis without protecting groups is worth mentioning.
Trans-decalin with two quaternary centers and oxabicyclo[3.2.1]octane with three quaternary centers are each constructed in a one-step cascade reaction.
The former reaction, in which the acylarene is cyclized to unsaturated aldehydes, is probably well known, but ideally used here.
They used Fe(ClO4)3 to find the conditions to get more than 50% yield. The reaction mechanism is explained in detail with calculations.
The only asymmetric source is the catalyst developed by Dr. Corey and his colleagues for the dihydroxylation of geranylacetone. Coincidentally, Dr. Corey has recently published a more effective catalyst for epoxidation. This paper may be one of the confirmations of the usefulness of the catalyst.
One of Professor Krische’s main topics is ruthenium-catalysed hydrogen auto-transfer. The isomerisation of benzocyclobutane to ortho-quinodimethane or hydroxyketone to enediol is a common reaction, so we need to look elsewhere to see what role ruthenium plays.
As they are experts in transition metal catalysts, we can see some rarely seen (and expensive-looking) catalysts. On the other hand, there are a few reactions that were finally successful after trying various conditions. The unsophisticated part of natural product synthesis makes me be relieved. This is the first asymmetric synthesis of a compound in this class. The key point, the asymmetric epoxidation, was found after several attempts.
Unfortunately, the axial chirality could not be unambiguously determined. However, the X-ray analysis of the two model compounds and the expected transition states suggest that the submitted structure must be incorrect.
不安定なブリッジヘッドエノンをジエノファイルとするIMDAを鍵段階とする高度に酸化されたent-カウラン類の全合成です。６員環上に２つの４級中心ができます。素晴らしい。反応はジラジカルを中間体として[4+2]体（Major)と[2+2]体の混合物になりますが，[2+2]体を一電子還元して[4+2]体に変換できるというところが最大の見せ場です。一般的に使える反応ならおもしろい。
反応機構と選択性について，DF計算でうまく説明しています。
later stageでの官能基化では２つのアリル酸化（PDCとSeO２)を有効に使ってます。
The total synthesis of highly oxidized ent-Kauranes was achieved with IMDA as the key step. The unstable bridgehead enone was used as the dienophile, creating two quaternary centers on the six-membered ring. Excellent. The reaction product is a mixture of [4+2] (major) and [2+2], resulting from diradical intermediates. The best part of the synthesis may be that the [2+2] can be converted to [4+2] by one-electron reduction. It would be interesting if the reaction could be used in general.
The reaction mechanism and selectivity are well explained by DF calculations.
Two allyl oxidations (PDC and SeO2) were effectively used in the later functionalization step.
A short step synthesis is achieved by a convergent pathway in which the central D-ring is constructed with IMDA.
As the dienophile is acetylene, the product is unconjugated cyclohexadiene, which is easily aromatised and convertible to a saturated form related to natural products.
Eschenmoser fragmentation is successfully used for the synthesis of acetylenes in the DA precursor.
Thermal DA did not work, so conditions were investigated using Rh and Ni catalysts and optimised to allow aromatisation and deprotection to be carried out in one pot.
The synthesised 20-isoveratramine did not match the natural product. Synthesis of the corrected structure may be the next task.
Highlights.
The acyloin rearrangement related to the biosynthesis, allowed simultaneous synthesis of two types of limonoids.
The Nazarov reaction using Lewis acids didn’t work, so the milder photochemical alternative was used. Since iPrCOOH is added from the beginning, it seems that the interrupted Nazarov reaction, which intermolecularly traps the cation after cyclization, was assumed.
Although the 6π-electron cyclization occurred with the compound containing a conjugated diene, its synthetic precursor containing the hydroxyl group underwent the desired reaction. Unfortunately, the stereoselectivity was not in the desired direction. Light Nazarov is disrotatory, so the selectivity is a matter of inward or outward rotation. This is called “torque selectivity”.
They proved by calculation that if the hydroxyl group is methylated to prevent intramolecular hydrogen bonding in the transition state, the selectivity is reversed and the desired compound is obtained (inward rotation → outward rotation). Excellent.
The NHC-catalysed reactions were used in two places, and the benzoin (acyloin?) condensation via the Breslow intermediate is impressive.
There are interesting reactions in various places, e.g. the semipinacol rearrangement via cyclic phosphorane, ozone decomposition in the presence of Et3N and NMO, intramolecular Reformatsky using tellurium, practical acylative kinetic resolution, functional group transformation by redox reaction in the final step.
RCM was used to construct the 7/5 system stereoselectively and efficiently from MJA. For the 6/6 system, the precursor for an intramolecular DA could not be obtained, and cascade radical cyclization was impractical, including stereoselectivity, so they ended up achieving their goal by intramolecular PK + C1 ring expansion. From the resulting cage-like compound, they extended the side chain stereoselectively to reach the final product.
The alkylation of the ester α-position of MJA produces an quaternary chiral center via acyclic stereoselection. This finding makes MJA a useful starting material for natural product syntheses.
There are two basic skeletons in related compounds. The general construction of the 5/6/7-membered ring system was already reported in 2023 by the same author, and now the synthesis of the 5/7/6-membered ring has been established.
Although the synthetic method for each fragment is different, it is similar to the route of Furstner et al. (including the difficulty in the final oxidation). It is interesting to compare the two papers, including the failures leading to the pathway, to see the differences and similarities.
The 7-membered ring part was constructed with the royal aldol reaction. The only one that succeeded after trying various catalysts was Bu2BOTf, which is unprecedented. Good job.
The conversion of ineleganolide to hororide that Furstner et al. found were not reported here, but since various ene-dione compounds did not undergo C12 isomerization, it was proposed that the isomerization may occur through retro-Michael-Michael after oxa-MIchael.
You can enjoy the first stage, which focuses on skeletal construction, and the second stage, which focuses on functional group transformation, in a variety of ways.
I wish I had listened to it at the lecture.
The protecting group assumes multiple roles. Acetonide is also a protecting group for acetylene and has a conformational fixing role to make a 5/7 system. Epoxide is a precursor of diol, but it contributes to selective introduction of hydroxyl and acyl groups through hydrogen bonding. This is in contrast to the three membeed gem-dimethyl ring, which serves as a steric hindrance in the same upward side.
The multifunctional groups are crowded together, so orchestrating operations would be inevitable .
As an old-timer, I feel nostalgic as there are quotations in the old standard reactions.
uploaded (+)-Berkeleyacetal D and (+)-Peniciacetal I
https://www.ohira-sum.com/wp-content/uploads/2025/03/jacs25-5933.pdf
素晴らしい位置選択的な反応がたくさんありますが，求める選択性が得られなかったので，色々工夫しているところがおもしろいです。最後の圧巻がSETを経るアリル酸化（？）。苦労はこういう形でむくわれるものかもしれません。
選択性を逆転させたのは，IMDA(exo付加➞低温Lewis酸触媒でend付加），HAT還元による異性化(分子内1,5シフト➞官能基変換による抑制），ケトンα位脱プロトン化（MOMエノールエーテルとして保護），脱水(エキソ方向➞脱水素化，脱水，1,4還元でエンド方向），エポキシ化（混み合いの少ない方から➞溶媒でブロックし，混み合いの多い方から）。
最後のアリル位の酸化は，何を目論んでいたのかはわかりませんが，エノラート化の条件に付すと，分子内のredox反応（HBrの脱離）が起きて，あっという間に最終物ができます。反応機構についてはモデル化合物も使って詳しく検討しています。
Barton先生の古い論文の引用（フォトサントニン転位とか）がいくつかあります。
There are many wonderful regioselective reactions, but it is interesting to see how they invented different reactions because they could not get the selectivity they were looking for. The final highlight is the allyl oxidation (?) by SET. I am happy to see the hard work pay off in this way.
Reactions where the selectivity was reversed are IMDA (exo addition ➞ end addition at low temperature with Lewis acid catalyst), isomerization by HAT reduction (intramolecular 1,5 shift ➞ suppression by functional group conversion), ketone α-deprotonation (protection as MOM enol ether), dehydration (exo direction ➞ end direction by dehydrogenation, dehydration, and 1,4 reduction), and epoxidation (from less hindered side ➞ from more hindered side by blocking with the solvent).
I don’t know what they were planning for the oxidation of the allyl moiety at the end, but when it is subjected to enolate-forming conditions, an intramolecular redox reaction occurs (releasing HBr) and the final product is suddenly obtained. The reaction mechanism has been studied in detail using model compounds.
There are some references to old papers by Dr. Barton (e.g. the photosantonin rearrangement).
Uploaded Vallesamidine and Schizozygane Alkaloids
https://www.ohira-sum.com/wp-content/uploads/2025/03/jacs25-4613.pdf
two phase synthesis (環化酵素 + 酸化還元酵素)です。中間体の芳香環を酸化して各種関連天然物に導いています。
不斉クロスカップリングで作った，４級不斉中心を含み，４方向に選択的官能基変換可能なビルディングブロックの高い機能性を証明する全合成とも言えます。
レドックス触媒活性といわれるフタルイミドエステル使ったラジカル反応がレドックス条件下でうまくいかず，結局, AIBN-Bu3SnHでラジカル環化を成功させ, エチレンブリッジをつくっています。
ニトリルから１炭素伸長したカルボン酸等価体と分子内アミドを作る工程で苦労しましたが，最終的にはTosMICを使って効率的な経路にしました。
Two-phase synthesis (cyclase + oxidoreductase). Aromatic rings of intermediates are oxidized and converted to various related natural products.
It can be said that this is a total synthesis that demonstrates the high functionality of the building block produced by asymmetric cross-coupling. It contains a quaternary chiral center and all four functional groups that can be manipulated orthogonally.
The radical reaction with the phthalimide ester, which was expected to be active as a redox catalyst, failed under redox conditions. Finally, AIBN-Bu3SnH was used for successful radical cyclization to form an ethylene bridge.
They struggled with the process of making the amide by intramolecular condensation after a one-carbon extension of the nitrile. They finally succeeded in creating an efficient route to the amide using TosMIC.
uploaded Janthinoid A
https://www.ohira-sum.com/wp-content/uploads/2025/03/jacs24-26351.pdf
まず特筆すべきは保護基なしの14段階合成でしょう。
４級中心を２つ含むトランスデカリン，３つ含むオキサビシクロ[3,2,1]オクタンを，それぞれワンステップのカスケード反応で一挙に構築しています。
前者のアシルアレンが環化して不飽和アルデヒドになる反応，既知なんでしょうけど，理想的に使ってます。
後者のラジカル環化，発生したラジカルが共役によって，先の二重結合まで非局在化して，二重結合が異性化することができるので，環化も可能になります。Fe(ClO4)3を使って50%を超える条件を見つけています。また，計算で詳しく反応機構を説明しています。
不斉源はゲラニルアセトンのジヒドロ化に使ったCorey先生らの触媒のみですが，奇しくも，そのCorey先生が，より有効なエポキシ化の触媒をつい最近発表されています。その有用性を裏付けたということもできますね。
First of all, the 14-step synthesis without protecting groups is worth mentioning.
Trans-decalin with two quaternary centers and oxabicyclo[3.2.1]octane with three quaternary centers are each constructed in a one-step cascade reaction.
The former reaction, in which the acylarene is cyclized to unsaturated aldehydes, is probably well known, but ideally used here.
They used Fe(ClO4)3 to find the conditions to get more than 50% yield. The reaction mechanism is explained in detail with calculations.
The only asymmetric source is the catalyst developed by Dr. Corey and his colleagues for the dihydroxylation of geranylacetone. Coincidentally, Dr. Corey has recently published a more effective catalyst for epoxidation. This paper may be one of the confirmations of the usefulness of the catalyst.
Formicamycin H uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/03/jacs24-26351.pdf
Krische先生のメインテーマの一つはRuthenium-Catalyzed Hydrogen Auto-Transferとのこと。
ベンゾシクロブタン→オルトキノジメタンとかヒドロキシケトン→エンジオールの異性化は普通に起こりそうな反応ですが，ルテニウムがどういう役割をしているのか，別の所で勉強する必要があります。
あまりみかけない（高価そうな）遷移金属触媒触媒がちょこちょこと出てくるのは，さすが専門家ということでしょう。
一方，結構いろんな条件を試してやっとうまくいった反応がちらちらとにあって，天然物合成の泥臭さを感じ，ホッとします。このクラスの化合物では初の不斉合成とのことですが，ポイントである不斉エポキシ化もいろいろやって見つけたようです。
軸不斉の配置が疑いなく決定できなかったのは残念ですが，２つのモデル化合物のX線解析と予想される遷移状態から，提出構造は間違いであろうと推定しています。
One of Professor Krische’s main topics is ruthenium-catalysed hydrogen auto-transfer. The isomerisation of benzocyclobutane to ortho-quinodimethane or hydroxyketone to enediol is a common reaction, so we need to look elsewhere to see what role ruthenium plays.
As they are experts in transition metal catalysts, we can see some rarely seen (and expensive-looking) catalysts. On the other hand, there are a few reactions that were finally successful after trying various conditions. The unsophisticated part of natural product synthesis makes me be relieved. This is the first asymmetric synthesis of a compound in this class. The key point, the asymmetric epoxidation, was found after several attempts.
Unfortunately, the axial chirality could not be unambiguously determined. However, the X-ray analysis of the two model compounds and the expected transition states suggest that the submitted structure must be incorrect.
Diepoxy-ent-Kaurane uploaded
https://www.ohira-sum.com/wp-content/uploads/2025/02/jacs25-1197.pdf
不安定なブリッジヘッドエノンをジエノファイルとするIMDAを鍵段階とする高度に酸化されたent-カウラン類の全合成です。６員環上に２つの４級中心ができます。素晴らしい。反応はジラジカルを中間体として[4+2]体（Major)と[2+2]体の混合物になりますが，[2+2]体を一電子還元して[4+2]体に変換できるというところが最大の見せ場です。一般的に使える反応ならおもしろい。
反応機構と選択性について，DF計算でうまく説明しています。
later stageでの官能基化では２つのアリル酸化（PDCとSeO２)を有効に使ってます。
The total synthesis of highly oxidized ent-Kauranes was achieved with IMDA as the key step. The unstable bridgehead enone was used as the dienophile, creating two quaternary centers on the six-membered ring. Excellent. The reaction product is a mixture of [4+2] (major) and [2+2], resulting from diradical intermediates. The best part of the synthesis may be that the [2+2] can be converted to [4+2] by one-electron reduction. It would be interesting if the reaction could be used in general.
The reaction mechanism and selectivity are well explained by DF calculations.
Two allyl oxidations (PDC and SeO2) were effectively used in the later functionalization step.
uploaded (-)-Veratramine and (-)-20-iso-Veratramine
https://www.ohira-sum.com/wp-content/uploads/2025/02/jacs25-3010.pdf
真ん中あたりのD環をIMDAでつくるという収束的経路で短工程合成を達成しています。
ジエノフィルはアセチレンを使うので，生じるのは非共役シクロヘキサジエンとなり，芳香化が容易であると共に，飽和体へ還元して，多くの関連天然物への誘導が可能になります。
DA前駆体のアセチレン合成にはEschenmoser fragmentation が上手に使われています。
DAは熱ではうまくいかず，RhやNiの触媒で条件検討し，さらに芳香族化，脱保護までone potで進行させる所まで最適化しています。
合成した20-isoveratramineは天然物と合わなかったとのことです。訂正構造体の合成も次の仕事になるかもしれません。
関連化合物の合成
https://www.ohira-sum.com/wp-content/uploads/2024/01/jacs24-1825.pdf
https://www.ohira-sum.com/wp-content/uploads/2024/01/jacs23-25086.pdf
どちらもC環をナザロフで作る経路。AB環は皆さんWMケトン由来。
A short step synthesis is achieved by a convergent pathway in which the central D-ring is constructed with IMDA.
As the dienophile is acetylene, the product is unconjugated cyclohexadiene, which is easily aromatised and convertible to a saturated form related to natural products.
Eschenmoser fragmentation is successfully used for the synthesis of acetylenes in the DA precursor.
Thermal DA did not work, so conditions were investigated using Rh and Ni catalysts and optimised to allow aromatisation and deprotection to be carried out in one pot.
The synthesised 20-isoveratramine did not match the natural product. Synthesis of the corrected structure may be the next task.
Synthesis of related compounds.
https://www.ohira-sum.com/wp-content/uploads/2024/01/jacs24-1825.pdf
https://www.ohira-sum.com/wp-content/uploads/2024/01/jacs23-25086.pdf
In both routes, the C ring was made with Nazarov and the AB ring was derived from WM ketone.
uploaded Phragmalin and Khayanolide-Type Limonoids
https://www.ohira-sum.com/wp-content/uploads/2025/02/jacs25-3003.pdf
見どころ満載です。
acyloin rearrangementは生合成とも関わっており、2つのタイプの関連化合物の同時合成を可能にしています。
ルイス酸をつかうナザロフはうまくいかなかったので milder photochemical alternativeを検討します。最初からiPrCOOHを入れているので、環化後のカチオンを分子間でトラップするInterrupted Nazarovを想定していたようです。
共役ジエンを含む化合物では6π電子環化が起きたので、その合成前駆体の水酸基を含む化合物を使うと、目的の反応が起こりますが、立体選択性は望まない方向。光ナザロフは逆旋性なので、内向きにまわるか外向きにまわるかの選択性が問題になります。“Torquoselectivity”と言うらしい。
遷移状態で分子内水素結合が生じないよう水酸基をメチル化すると、選択性が逆転し，（内旋→外旋）望む化合物が得られる事を計算で証明しています。すばらしい。
NHCを触媒とする反応を二箇所で使っていますが、Breslow中間体を経るベンゾイン（アシロイン？）縮合が印象的。
環状ホスホランを経由するセミピナコール転位とか、Et3NとNMO共存下のオゾン分解、テルルを使う分子内Reformatsky, 実用的なacylative kinetic resolution、最終段階での酸化還元反応による官能基変換などなど、各所でおもしろい反応を見ることができます。
Highlights.
The acyloin rearrangement related to the biosynthesis, allowed simultaneous synthesis of two types of limonoids.
The Nazarov reaction using Lewis acids didn’t work, so the milder photochemical alternative was used. Since iPrCOOH is added from the beginning, it seems that the interrupted Nazarov reaction, which intermolecularly traps the cation after cyclization, was assumed.
Although the 6π-electron cyclization occurred with the compound containing a conjugated diene, its synthetic precursor containing the hydroxyl group underwent the desired reaction. Unfortunately, the stereoselectivity was not in the desired direction. Light Nazarov is disrotatory, so the selectivity is a matter of inward or outward rotation. This is called “torque selectivity”.
They proved by calculation that if the hydroxyl group is methylated to prevent intramolecular hydrogen bonding in the transition state, the selectivity is reversed and the desired compound is obtained (inward rotation → outward rotation). Excellent.
The NHC-catalysed reactions were used in two places, and the benzoin (acyloin?) condensation via the Breslow intermediate is impressive.
There are interesting reactions in various places, e.g. the semipinacol rearrangement via cyclic phosphorane, ozone decomposition in the presence of Et3N and NMO, intramolecular Reformatsky using tellurium, practical acylative kinetic resolution, functional group transformation by redox reaction in the final step.
Uploaded (+)-Mannolide B
https://www.ohira-sum.com/wp-content/uploads/2025/02/jacs25-0636.pdf
7/5系は，RCMを使い，MJAから立体選択的，効率的に構築できました。しかし，6/6系では，分子内DAの前駆体ができず， カスケードラジカル環化では立体選択性も含めて非実用的ということで，結局，分子内PK＋C1環拡大で目的を達成しました。できた籠状化合物から立体選択的に側鎖を伸ばし，最終物まで誘導しています。
MJAのエステルα位をアルキル化すると，非環状立体選択的に４級不斉中心ができるという知見は,MJAの出発原料としての一つの有用性となっています。
RCM was used to construct the 7/5 system stereoselectively and efficiently from MJA. For the 6/6 system, the precursor for an intramolecular DA could not be obtained, and cascade radical cyclization was impractical, including stereoselectivity, so they ended up achieving their goal by intramolecular PK + C1 ring expansion. From the resulting cage-like compound, they extended the side chain stereoselectively to reach the final product.
The alkylation of the ester α-position of MJA produces an quaternary chiral center via acyclic stereoselection. This finding makes MJA a useful starting material for natural product syntheses.
uploaded Scabrolide B, Ineleganolide
https://www.ohira-sum.com/wp-content/uploads/2025/01/jacs25-0130.pdf
関連化合物として２つの基本骨格がありますが，５/6/7員環系の一般構築法はすでに2023年に報告しており，今回5/7/6員環の合成を確立しました。
各フラグメントの合成法は異なるものの，先に発表されたFurstnerらの経路と似たものになっています。（最後の酸化で苦労するあたりも）
その経路に至るまでの失敗なども含めて，２つの論文を比較すると，違う所や同じ所が見えて，面白いです。
https://www.ohira-sum.com/?cpage=7
https://www.ohira-sum.com/wp-content/uploads/2024/10/jacs24-24250.pdf
７員環部分を王道のアルドール反応でやってます。種々触媒を試して唯一成功したのが，例のないBu2BOTf。よかったー。
Furstnerらが見つけたIneleganolideからHororideへの変換については報告してませんが，種々のエン-ジオン化合物がC12異性化をおこさなかったことから，異性化はoxa-MIchael の後，retro-Michael-Michaelで起こるのではないかと提案しています。
There are two basic skeletons in related compounds. The general construction of the 5/6/7-membered ring system was already reported in 2023 by the same author, and now the synthesis of the 5/7/6-membered ring has been established.
Although the synthetic method for each fragment is different, it is similar to the route of Furstner et al. (including the difficulty in the final oxidation). It is interesting to compare the two papers, including the failures leading to the pathway, to see the differences and similarities.
https://www.ohira-sum.com/?cpage=7
https://www.ohira-sum.com/wp-content/uploads/2024/10/jacs24-24250.pdf
The 7-membered ring part was constructed with the royal aldol reaction. The only one that succeeded after trying various catalysts was Bu2BOTf, which is unprecedented. Good job.
The conversion of ineleganolide to hororide that Furstner et al. found were not reported here, but since various ene-dione compounds did not undergo C12 isomerization, it was proposed that the isomerization may occur through retro-Michael-Michael after oxa-MIchael.
Uploaded Euphorbialoid A
https://www.ohira-sum.com/wp-content/uploads/2024/12/jacs24-34221.pdf
骨格構築が中心の第一ステージも，官能基変換が中心の第二ステージもいろいろと楽しむことができます。
講演会でで聞いてみたかった。
保護基が複数の役目を負っています。アセトニドはアセチレンの保護基でもあったり，5/7系をつくるためのコンフォーメーション固定の役割を持ちます。エポキシドはジオールの前駆体ですが，水素結合を通して選択的な水酸基やアシル基導入に寄与します。同じ上向き三員環でもgem-dimethyl環が立体障害として役立っているのと対照的。
多官能基で混み合っているから，必然的にorchestrating operationになるのでしょう。
古い定番の反応にちゃんと引用があるので，古い人間としてはなつかしく，心地よいです。
You can enjoy the first stage, which focuses on skeletal construction, and the second stage, which focuses on functional group transformation, in a variety of ways.
I wish I had listened to it at the lecture.
The protecting group assumes multiple roles. Acetonide is also a protecting group for acetylene and has a conformational fixing role to make a 5/7 system. Epoxide is a precursor of diol, but it contributes to selective introduction of hydroxyl and acyl groups through hydrogen bonding. This is in contrast to the three membeed gem-dimethyl ring, which serves as a steric hindrance in the same upward side.
The multifunctional groups are crowded together, so orchestrating operations would be inevitable .
As an old-timer, I feel nostalgic as there are quotations in the old standard reactions.